Abstracts

The underlying pathomechanisms of epileptogenesis, the process leading to manifestation of epilepsy, are still not understood. An intriguing aim is to control acquired epilepsy by preventing epileptogenesis. Furthermore, the effects of epilepsy on cognitive function and behavior are of great interest because of their impact on patients[apos] quality of life. Rats with spontaneous seizures developing after status epilepticus (SE) are known to exhibit behavioral alterations and therefore are a good tool to study the influence of antiepileptic drugs on behavior. The aim of the present study was to investigate if valproate (VPA) prevents development of epilepsy with spontaneous recurrent seizures (SRS) in a post-SE model of temporal lobe epilepsy (TLE). Furthermore we investigated whether VPA treatment reduces the behavioral alterations associated with epilepsy. For this purpose, female Sprague Dawley rats received a prolonged electrical stimulation of the basolateral amygdala which resulted in the development of a self-sustained SE. We limited SE duration to 4 h by diazepam and started VPA treatment immediately thereafter. VPA was administered as a bolus injection of 400 mg/kg and thereafter three times daily at 200 mg/kg for four weeks. A vehicle group was formed from rats treated with saline. Four weeks after drug treatment, the occurrence of SRS was monitored by continuous video/EEG-recording for one week. Five weeks after drug treatment the rats were tested in a battery of behavior tests including elevated plus maze, morris water maze, open field, rotarod, and a postseizure behavioral battery. During prolonged treatment, VPA exerted anticonvulsant activity. However, four weeks after treatment, vehicle- and VPA-treated rats showed about the same number of SRS. These data indicate that VPA does not exert any anti-epileptogenic effect in the TLE model chosen for the present experiments. Furthermore VPA-treated rats showed the same cognitive deficits as the vehicle-treated group. The time spent on open arms at the elevated plus maze was significantly higher in the vehicle-group compared to VPA-treated rats and rats without epilepsy (control group). In the open field vehicle-treated rats spent significantly more time in the center and exhibited significantly higher locomotion and exploration behavior compared to the two other groups. In the postseizure behavioral battery, both, vehicle- and VPA-treated epileptic rats, exhibited a significantly higher score in the [ldquo]touch-response test[rdquo] compared to the control group, whereas the VPA-treated rats were less reactive than vehicle-treated rats. These findings indicate that SE and SRS induce abnormal behavior as the rats are hyperexcitable, show higher locomotion and exploration, and show reduced anxiety-related behavior. VPA treatment counteracts these behavioral alterations.